title: Anti-M(3) muscarinic cholinergic autoantibodies from patients with primary Sjögren's syndrome trigger production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E(2) (PGE(2)) from the submandibular glands.
abstract: BACKGROUND
  We demonstrated that serum immunoglobulin G (IgG) from patients with primary Sjögren's syndrome (pSS), interacting with the second extracellular loop of human glandular M(3) muscarinic acetylcholine receptors (M(3) mAChR), trigger the production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E(2) (PGE(2)).
  
  
  METHODS
  Enzyme-linked immunosorbent assays (ELISAs) were performed in the presence of M(3) mAChR synthetic peptide as antigen to detect in serum the autoantibodies. Further, MMP-3 and PGE(2) production were determined in the presence of anti-M(3) mAChR autoantibodies.
  
  
  RESULTS
  An association was observed between serum and anti-M(3) mAChR autoantibodies and serum levels of MMP-3 and PGE(2) in pSS patients. Thus, we established that serum anti-M(3) mAChR autoantibodies, MMP-3 and PGE(2) may be considered to be early markers of pSS associated with inflammation. Affinity-purified anti-M(3) mAChR peptide IgG from pSS patients, whilst stimulating salivary-gland M(3) mAChR, causes an increase in the level of MMP-3 and PGE(2) as a result of the activation of phospholipase A(2) (PLA(2)) and cyclooxygenase-2 (COX-2) (but not COX-1).
  
  
  CONCLUSIONS
  These results provide a novel insight into the role that cholinoceptor antibodies play in the development of glandular inflammation. This is the first report showing that an antibody interacting with glandular mAChR can induce the production of pro-inflammatory mediators (MMP-3/PGE(2)).
authors.affiliation: Pharmacology Unit, School of Dentistry, University of Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Reina
authors.forename: Leonor
authors.initials: L
authors.lastname: Sterin-Borda
authors.forename: Daniela
authors.initials: D
authors.lastname: Passafaro
authors.forename: Enri
authors.initials: E
authors.lastname: Borda
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D002846:Chromatography, Affinity; D051546:Cyclooxygenase 2 / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D019278:Matrix Metalloproteinase 3 / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D011976:Receptors, Muscarinic / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism; D013363:Submandibular Gland / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D011976:Receptors, Muscarinic; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019278:Matrix Metalloproteinase 3